Controlling The Brain With Light

The excerpt below comes from Forbes/Wolfe Emerging Technology Report’s recent full-length interview with Dr. Ed Bodyen, one of the world's leading neuroscientists. We learn about the fascinating new technique of optogenetics, which enables us to control the brain with light.

Ed Boyden is the Benesse career development professor and associate professor of biological engineering and brain and cognitive sciences, at the MIT Media Lab. He leads the Synthetic Neurobiology Group, which develops tools for controlling and observing the dynamic circuits of the brain, and uses these neurotechnologies to understand how cognition and emotion arise from brain network operation, as well as to enable systematic repair of intractable brain disorders such as epilepsy, Parkinson’s disease, post-traumatic stress disorder and chronic pain. Ed received his Ph.D. in neurosciences from Stanford University as a Hertz Fellow, where he discovered that the molecular mechanisms used to store a memory are determined by the content to be learned. Before that, he received three degrees in electrical engineering and physics from MIT. He has contributed to more than 200 papers, current or pending patents and articles, has given over 100 invited talks, and writes an occasional column for Technology Review magazine.

Tell us a bit about your professional background.

I direct a neurotechnology department here at MIT. Our goal is to figure out how to map and control the circuits of the brain. We love to find ways to build technologies that allow us to put neuroscience on really firm, concrete footing; the way that other molecular biology fields that are really concentrated on medicine.

What specifically is your group working on?

About a third of the group works on technologies from mapping the brain, about a third for recording from the brain and a third for controlling the brain. We work backwards from the physical principles of the brain, survey all the laws of physics and chemistry and engineering and so on and then synthesize those fields in order to develop ways to map and control and record things. We have more than 40 full-time people and about a dozen undergrads and volunteers. We collaborate people in hundreds of different groups all over the world on active technology involving projects.

Tell us a bit about the field of optogenetics.

Optogenetics is a technology that lets you turn on or off the cells of the brain. The cells compute using electricity, and otptogenetic molecules are essentially genetically encoded solar cells powered by electricity. We insert these molecules in neurons and we then have the ability to turn those neurons on or off by shining light on them.

How was this field discovered?

I was a first year graduate student at Stanford and I was really interested in this class of molecules that capture light and transform it into signals that our brain can understand. So, it turns out that organisms all over the tree of life have these kinds of molecules. Around early 2000, I got really interested in using them as a potential way of controlling neurons. That Spring I started collecting these molecules. In 2004, I was a graduate student in Dick Chen’s group and collaborating with a post-doctoral scholar, Carl Reistrov. The two of us got together and put the molecules into neurons and found that when I would flash light on the cell, it activated it. That is, it would fire and electrical spike.

This was the birth of optogenetics?

Yes, that was the beginning. It was just sheer serendipity that we discovered by putting this molecule into neurons at the right speed, the right magnitude effect, it had the right expression quality and the ability to express safely—it worked. Very quickly, we published this paper and hundreds and hundreds of groups started using the molecule.

Ever since then we’ve been trying to expand and improve our toolbox. In that first paper, we could activate neurons with blue light. In 2007 my group, now at MIT, showed we could silence neurons with yellow light. In 2010, we showed we could silence neurons more powerfully because it turned out to be really hard to quiet down neurons. Then in 2011, we improved the silencer still further.

Earlier this year, we published the multicolor technology for activating different neurons with different colors of light, which is really important. You would activate a reward pathway with one color of light, for example, and you could activate some kind of sensory information with the second light and see how learning occurs. Finally, a couple weeks ago we published non-invasive optogenetics that turn neurons off using red light and red light, of course, goes deeper in the body than other colors.

What types of organisms are you studying?

We work on all the organisms of neuroscience. We do work on worms, flies, and we’re often working collaborators of course. In 2009, for example, anticipating that these tools might be of interest for not just studying the brain, but also as potentially for a treatment in humans, we started the first non-human primate clinical work with optogenetics as well.

Why is it significant that you can activate certain neurons in the brain?

Thousands of groups are using our tools for everything, including driving pathways in the brain that cause reward; you can activate certain pathways in the brain and make the brain do more of whatever it’s just doing. There’s a group at Caltech that’s activated neurons in the brain that drive violence or aggression. You can activate certain neurons and mice will attack things in front of them, even a glove.

Others are activating cells in the brain to try to figure out how smells and odors are encoded. A group at Columbia University, for example, showed that by activating smell cortex neurons you could actually condition smells to be positive or negative. Smell might be very plastic; that is you can change it.

What exactly are you doing to modify the brain to make it responsive to light?

We put a virus in the brain that encodes for that gene. The neurons then manufacture the light-sensitive protein. We shine light on the area, and only the neurons that are expressing the protein will be activated or silenced. You can activate just the subset of neurons within an area that are of a certain kind. So, within a cubic millimeter of brain tissue you might have thousands of different kinds of neurons and yet specific neurons are differentially impaired.

What we want to do is control the brain with its native language. We want to be able to really understand the neural code at such a deep level that we can understand what a thought is, or a feeling is, and then be able to fix problems of cognition and neurology and psychiatry.Do you think we’ll be able to solve the human brain in our lifetime?

We certainly hope to build technologies to make that feasible, but it’s also important to realize that in any pre-paradigmatic science, knowing exactly where the finish line is is difficult. The way our mission is framed, over the next few decades, we’d like to build the tools that allow the understanding of the brain.

What excites you the most in what you’re doing in your lab?

I’m very excited about these new kinds of microscopes that we’re building that allow you to map all the neural activity in a complete organism. I think that’s going to be very interesting. If we could understand all the biophysical mechanisms and all the information processing of a small organism, I think that would yield some really fundamental insights into how biological systems work. I also think that our ability to control neurons is becoming unprecedentedly powerful and that’s also very interesting to me.

Finally, I think we’re really trying to figure out how to build practical human technologies as well. Last year, for example, three of our groups got together and we published a paper going through all the laws of physics to figure out every possible way you could interact with the brain. We were able to really pinpoint some very promising avenues that might allow you to record and control neural activity with precision, but maybe even in ways that are human compatible.